The primary objectives are: (a) the chemical synthesis of conjugates of alpha-amanitin to macromolecules of defined antigenic potential (bovine serum albumen, Keyhole limpet hemacyanin, bacterial flagellin, bovine immunoglobulin G), to characterized peptide hormones (ACTH, insulin, calcitonin, and lutenizing hormone) and to characterized lectins and mitogens (concanavalin A, pokeweed mitogen); b) the chemical characterization of these conjugates with respect to tertiary structure and determination of number of moles of alpha-amanitin bound per mole of macromolecule; c) the determination of K1 values for each conjugate with calf thymus RNA polymerase II to compare each with free alpha-amanitin with respect to inhibitory potential; and d) the comparison of each to inhibit RNA synthesis, DNA synthesis, and cell division in vitro (e.g. mouse L cells, human amnionic AV-3 cells, human lymphoblastoid cells, mouse T cell populations, mouse B cell populations, mouse macrophages) and in vivo (mice). Alpha-Amanitin will be conjugated to the various macromolecules via a spacer using established procedures. The macromolecule-amanitin conjugates will be characterized using circular dichroism and chemical titration of free amino and carboxyl groups to assess the effects of conjugation on the tetiary structure of the carrier. The determination of the K1 values of the various conjugates and free alpha-amanitin with calf thymus DNA dependent portion of the conjugate on the inhibitory potential of the amanitin toward nuclear RNA synthesis. The inhibitory potential of the various conjugates toward specific cell types will be determined by measuring their effects on the incorporation of labelled thymidine and/or uridine into acid insoluble material, and by determining the effect of each conjugate on cell growth.